The objective of our research is elucidation of the molecular mechanisms of important heme and non-heme proteins both isolated and in intact cells using the techniques of magnetic resonance spectroscopy. It is our belief that an accurate knowledge of the mechanisms of protein function is fundamental to an understanding of the molecular basis of life and may be essential for dealing with health related problems arising from molecular abnormalities. We propose to study the mechanism of cooperative oxygenation of hemoglobin, the mechanism of gelation of sickle hemoglobin, the arrangement and conformation of substrates at the catalytic sites of several kinases and synthetases, the role of metal ions in the catalysis of phosphoryl transfer, the arrangement of substrates and products at the active site of carbonic anhydrase, the electron transfer mechanism of cytochrome c and its ion-binding properties, the existence and conformation of an iron-bleomycin-DNA complex, the effect of insulin on cellular ion-transport processes, and a possible regulatory role of ionized Mg 2 ion in cellular metabolism. A secondary objective of our research is the development of new methodology and/or refinement of existing magnetic resonance methods for the study of biological systems.